We have been successful in growing human cancer cells in immunosuppressed rats, as a solid subcutaneous tumor nodule. HeLa TCRC-1 and HeLa TCRC-2 are monophenotypic for the expression of the trophoblast gene products, Regan (placental) and non-Regan (chorion) isoenzyme of alkaline phosphatase respectively. Both of these cell lines undergo phenotypic alteration in their isoenzyme profile, while growing in animals. A new onco-amnion (FL) isoenzyme is expressed in both of these cell lines. The present application proposes to study this phenomenon in detail. For example, the role of the host animal, and the method of immunosuppression will be investigated with respect to isoenzyme expression. Immuno-incompetent animals, and immuno-privileged sites will be explored for their role in isoenzyme expression of human tumor xenografts, in the absence of immunosuppression. The effects of in vivo growth of a variety of human tumors evidencing Regan and other known tumor markers will also be examined. Finally, we will apply standard methods of isoenzyme regulation in cultured cells to the study of isoenzyme expression in human tumors growing in animal hosts. Such an animal model system may be helpful in bridging the gap between data obtained in tissue culture, and the growth of human tumors in their syngeneic human host. More importantly, this model system may permit us to investigate the regulation of developmental gene expression in human cancer cells.